The ability to test hypotheses in a variety of neuroscience fields has expanded exponentially due to new and emerging technologies that detect and probe molecular, cellular and physiological events in terminally collected samples or living model organisms with ever increasing power and capabilities. Supported by an NINDS P30 grant since 2003, the University of California San Diego Neuroscience Microscopy Imaging Core has grown into a world-class core and a centerpiece for local neuroscience research. Importantly, the Core serves an otherwise unmet neuroscience research need in microscopy imaging of many laboratories. Its existence has resulted in remarkable yields in productivity, expanded scientific scope and ability to test hypotheses using cutting edge technologies. In this application, we seek to acquire a Zeiss Lightsheet Z.1 microscope for fast, gentle, multiview imaging deep into thick samples such as cleared brain and spinal cord tissue blocks or living organisms. The requested system was chosen because of the high quality of data that it generates, unsurpassed abilities to document events in the nervous system not previously feasible and its ease of use, which is critical for a multi-user core. In addition, we ask for funds to help maintain, operate and support a number of existing cutting edge imaging tools at the Core. On top of 35 NINDS-funded Major User labs with 44 qualifying projects, a wider base of neuroscience investigators benefit from access to our Core. UCSD is a leading institution in neuroscience research, with our neuroscience graduate program consistently ranked among the top in the nation. The strong support of local neuroscience researchers along with that of institutional leadership, the synergies and the economies of scale that the Core has created and the continued P30 grant support will ensure the future success of our Core. In return, our Core supports the mission of the NINDS by serving a wide range of outstanding research programs that aim to gain fundamental knowledge of the nervous system and to reduce the burden of neurological diseases.